A Simple Clinical Test Could Make It Easier to Track
and Treat Alzheimer's

(Philadelphia,
PA) - A urine sample taken at the doctor's office can
be the step in determining your chances of developing
Alzheimer's disease (AD), according to researchers at
the University of Pennsylvania School of Medicine.
They have determined that a urine test can reliably
detect free radical damage associated with people with
Mild Cognitive Impairment (MCI) - a recognized precursor
to AD. The test detects isoprostanes, fatty acids that
are formed as the result of free radical damage in the
brain - damage that correlates with clinical diagnosis
of AD.

"This is the first noninvasive test that can predict
a clinical diagnosis of Alzheimer's disease," said
Domenico Praticò, MD, assistant professor
in Penn's Department of Pharmacology. "Since there
is no cure for Alzheimer's disease, physicians could
slow the course of the disease if it is caught early
enough."

Within four years of initial diagnosis, up to 50% of
people with MCI develop Alzheimer's disease. As AD progresses,
it attacks the brain and causes severe damage in the
areas important for memory, judgement, and language.
This destruction leads to other clinical complications
and, eventually, death.

In the study, published in the June edition of Archives
of Neurology, Praticò and his colleagues
measured isoprostane in blood and urine samples obtained
from 50 patients with a clinical diagnosis of AD, 33
patients with MCI, and 40 healthy volunteers. Two weeks
later, a CSF sample and a second urine sample were taken
from 28 of the AD patients, 17 of the MCI patients,
and 18 of the control subjects. The researchers found
significantly higher levels of isoprostane in CSF, blood,
and urine of MCI and AD subjects than in the volunteers.
Remarkably, the samples taken from the MCI subjects
and the volunteers differed only in respect to their
isoprostane levels.

"We found that patients with MCI have increased
brain oxidative damage before the onset of AD - damage
that can be detected in the form of isoprostanes in
urine, as this study shows," said Praticò.
"In fact, five MCI subjects, all with high isoprostane
levels, converted to AD during follow-up."

Patients that are diagnosed with Mild Cognitive Impairment
typically present their physicians with persistent memory
loss that is not normal for someone of their age and
education. Although their memory is impaired, MCI patients
are capable of living largely independent lives. At
this stage, it is difficult to determine whether a person
with MCI will eventually have Alzheimer's or whether
they will progress to a form of unrelated dementia.

A urine sample taken in the doctor's office may be a
first point of decision in gauging the risk of developing
AD. Further tests could then determine the severity
of a patient's condition and course of treatment. For
example, studies have shown that the transition from
MCI to AD occurs fastest in people who have a gene called
apoE4 and whose brain's hippocampus region is shown
to be smaller as measured in an MRI scan.

"One hypothesis is that, in AD, healthy brain tissue
is damaged by the local formation of large amounts of
free radicals," said Praticò. "Isoprostanes
are the byproducts of fats in the human body that were
warped by free radical attack. They then accumulate
in CSF, blood, and urine as the body works to get rid
of them."
While at the moment this test is not yet clinically
available, the team is working on the development of
a version of it that could be broadly and easily performed.

Unlike a spinal tap, a urine test is simple to do and
provides a painless and noninvasive way of assessing
the situation. "The advantages are clear: with
an easier test, doctors can diagnose the disease sooner
and respond better to the patient's needs," said
Praticò.
This research was supported by grants from the National
Institutes of Health and the American Heart Association.
Trial participants were selected at the Memory Disorders
Clinic of Penn's Alzheimer's Disease Center.

# # #

Editor's Note:

The University of Pennsylvania School of Medicine
& Health System provide international leadership
in biomedical research, medical education and quality
care. The School of Medicine ranks second among all
American medical schools receiving funds from the National
Institutes of Health and fourth among research medical
schools in the annual US News & World Report survey.